It is well established that histone acetylation is associated with transcriptional activity in eukaryotic cells. Acetylated core histones are known to preferentially associate with transcriptionally active chromatin. Acetylation occurs at lysine residues on the amino-terminal tails of histone proteins, thereby neutralizing the positive charge of the histone tails and decreasing their affinity for DNA. As a consequence, histone acetylation alters nucleosomal conformation, thereby increasing the accessibility of transcriptional regulatory proteins to chromatin templates.
Despite advances in identifying the large number of proteins having histone acetyltransferase or histone deacetylase activity and deciphering their roles in regulating gene expression, there is currently no way of modifying histone acetylation at specific locations. Although sodium butyrate is used to inhibit histone deacetylase activity, thereby indirectly increasing histone acetylation, this method of histone acetylation is global and non-specific. Acetylation, at essentially all locations, is modified. A need exists, therefore, for targeted histone acetylation. In particular, there is a need for means to target histone acetylase activity to specific chromosomal sequences such that histone proteins associated with the chromosomal sequence of interest can be acetylated.